Exploring the effect of temperature on a
mechanochemical reaction by in situ synchrotron
powder X-ray diffraction
Krunoslav Užarević*,a Vjekoslav Štrukil,a Cristina Mottillo,b Patrick A. Julien,b Andreas Puškarić,a
Tomislav Friščić*,b Ivan Halasz*a
a
Ruđer Bošković Institute, Bijenička cesta 54, HR-10000, Zagreb, Croatia;
b
Department of Chemistry and FRQNT Centre for Green Chemistry and Catalysis, McGill University,
Montreal, H3A 0B8 Canada
ABSTRACT: We describe the first in situ and real-time study of a mechanochemical reaction by variabletemperature synchrotron powder X-ray diffraction. Using the dry milling synthesis of a coordination
polymer as a model system, we reveal a change in reaction mechanism if temperature is increased and a
strong dependence of the reaction rate on temperature, with a ca. 6-fold increase of the rate of reactant
depletion for a 45 °C rise in temperature. These experiments provide also the first direct evidence how a
formally dry milling reaction is facilitated by water released from a hydrated reactant.
INTRODUCTION
Mechanochemical reactions,1-4 conducted by milling, grinding or shearing5-6 are rapidly emerging as an
attractive, clean, energy- and materials-efficient7,8 alternative to conventional solution-based synthesis of
a wide range of materials, from supramolecular and organic soft materials,9-13 to inorganic,14-20 organic,2127
organometallic28-34 and coordination compounds.35-41 Besides providing a solvent-free reaction
environment permitting chemical reactivity independent of reactant or product solubility,42
mechanochemistry also provides notable emergent synthetic advantages, including excellent control over
product stoichiometry and access to materials and chemical transformations that are difficult to achieve
by conventional synthetic methods.43-45
Growing interest in milling mechanosynthesis has highlighted a lack of knowledge of underlying
mechanisms and reaction kinetics. Whereas the effect of temperature on chemical reactivity has been
thoroughly investigated for a wide range of solution, gas and solid-state reactions,46 there is little
information on temperature dependence of milling reactions.47,48 It is, however, known that conducting a
mechanochemical reaction at an elevated temperature, e.g. by pre-heating the milling equipment, can have
a strong effect on the composition and structure of the resulting product.49 Nevertheless, studies of
temperature and thermal effects in ball milling reactions are rare,50-53 and most have focused on highly
exothermic mechanochemical self-propagating reactions.54-60
One reason why the effect of temperature on kinetics of mechanochemical milling reactions has
remained largely unexplored lies in the inability to follow mechanochemical reactions at a given
temperature directly, without the need to interrupt milling and extract samples for analysis. Very recently,
we have developed a technique for direct, real-time and in situ monitoring of mechanochemical reactions
using synchrotron X-ray powder diffraction. This technique uses highly penetrating high-energy X-rays
(λ  0.14 Å, E  86 keV) to obtain powder X-ray diffraction (PXRD) data from a sample while it is
mounted on an operating mill, allowing qualitative61 and quantitative62 assessment of the reaction
progress.45,63-65
We now present the first variable-temperature in situ X-ray diffraction study of a mechanochemical
reaction, using as a model system the assembly of coordination polymers of cadmium chloride with the
ditopic ligand cyanoguanidine (cnge).66 Reactions were performed using a thermally-insulated vessel
equipped with thermal sensors that also permitted in situ diffraction studies. The results of this proof-ofprinciple study, which creates an entirely new opportunity to study the course and heat exchange in ball
milling mechanochemistry, reveal a surprisingly strong effect of temperature on the reaction course and
kinetics.
Scheme 1. Mechanochemical reactions between CdCl2 and cyanoguanidine (cnge)
Mechanochemical milling reaction of CdCl2 and cnge was previously studied ex situ by PXRD66 and
in situ by Raman spectroscopy,63 making it a suitable model system. It was previously established that
milling of the two components in either 1:1 or 1:2 respective stoichiometric ratio can give rise to two
distinct coordination polymers, the one-dimensional (1-D) Cd(cnge)2Cl2 (1) and three-dimensional (3-D)
Cd(cnge)Cl2 (2, Scheme 1).
RESULTS AND DISCUSSION
The herein described reactions were conducted by neat grinding, i.e. without any auxiliary liquid
additives. Reaction progress was monitored in situ at the high-energy X-ray beamline ID15B of the
European Synchrotron Radiation Facility (ESRF), as described previously. 61 To enable quantification of
the reaction mixtures by Rietveld analysis, crystalline silicon was added as an internal scattering
standard.62 For experiments at elevated temperatures, carefully weighed reactants placed each in one half
of the vessel, and pre-heated in an oven together with the milling media. After being heated to a desired
temperature, the reaction vessel was closed and placed in a thermally insulating and non-diffracting casing
before being mounted on an in-house modified Retsch MM200 mill. Data was collected with a typical
time resolution of 9 seconds.
The experimental hutch of the ID15B beamline was air-conditioned to 20.5 C. Control over reaction
temperature is challenging as it requires precise balance of heat generated by mechanical friction of
milling media, and heat loss to the cooler environment of the experimental hutch. Without the latter,
frictional heating would cause continuous temperature increase inside the milling vessel. A sophisticated
methodology for controlling the reaction vessel temperature, e.g. by using an external flow cooling jacket,
was not practical as it would severly limit the ability for in situ collection of X-ray diffraction data.
Reaction vessels were manufactured from polymethylmetacrylate (PMMA),61 itself a good thermal
insulator (≈ 0.17 W m–1 K–1), and additionally closed within a thermally insulating casing (Scheme S1).
Temperature of the milled reaction mixture was measured by a rapid-response K-type thermocouple
embedded in the milling vessel wall, close to the internal surface. Good thermal contact between the
thermocouple and the vessel wall was ensured by thermally conducting paste. Temperature readings from
the thermocouple were automatically written to a file concomitantly with recording of X-ray diffraction
images. Reaction mixtures in all experiments were initially aimed to contain cnge and CdCl2 in a 2:1
stoichiometric ratio, targeting the formation of 1. However, subsequent data analysis revealed that initially
anhydrous CdCl2 had partially transformed into the corresponding monohydrate CdCl2·H2O during
transport and storage. Although unexpected, this deviation from the initial experiment design enabled the
in situ observation of remarkably different reactivity of anhydrous CdCl2 and its monohydrate.
Nominally room temperature (RT) milling experiments were conducted using two types of milling
media. In one case, two stainless steel balls of 7 mm diameter were used (1.34 g each, sample/media
weight ratio of 0.15), and in another a single stainless steel ball of 9 mm diameter (2.9 g, sample/media
weight ratio of 0.14). Simultaneous temperature and PXRD measurements revealed a different increase
in reaction temperature with time, as well as different reaction rates for the two experimental set-ups
(Figure 1). Upon milling with two 7 mm balls (Figure 1a), the temperature of the reaction mixture rose
from 23 °C to 26 °C over 30 minutes milling. During the first 20 min milling the reaction mixture
underwent amorphization, evidenced by the gradual loss of intensity of reactant diffraction lines. At ca.
20 min, diffraction lines consistent with those expected from the known structure of 1 appear (CCDC
code MAKXON).
Upon milling with a single 9 mm ball, (Figure 1b), the bulk temperature of the reaction mixture rose
from 24 °C to 32 C within 10 minutes. Quantitative Rietveld analysis confirmed that the
mechanochemical reaction in both cases proceeds via amorphization, first of anhydrous CdCl2, then of
CdCl2·H2O, and finally of cnge (Figures S1, S2).67 Based on Rietveld analysis, the first diffraction signals
of 1 appear after ca. 50 % of the reaction mixture becomes amorphous. Previous in situ study by Raman
spectroscopy revealed a similar reaction mechanism, where 1 was formed directly from reactants.63 Partial
melting and formation of a eutectic phase is unlikely since the reaction mixture remains in form of a freeflowing powder during milling. Comparison of quantitative reaction profiles reveals that the reaction
using a 9 mm ball proceeded ca. 3 times faster. The faster formation of 1 when using a heavier milling
ball reveals that the reaction rate is not related to the sample-to-media weight ratio. Such conclusion is
consistent with the previous ex situ study of this reaction.66
Figure 1. Time-resolved powder X-ray diffractograms (top) and associated temperature profiles
(bottom) for the mechanochemical reaction at room temperature using: (a) two stainless steel balls of 7
mm diameter and (b) one stainless steel ball of 9 mm diameter. The simulated PXRD pattern for the
expected coordination polymer product 1 (CCDC code MAKXON) is shown on top of each time-resolved
diffractogram, and the position of the (111) X-ray reflection of the internal diffraction standard crystalline
silicon is marked with ‘*’.
Room temperature in situ monitoring experiments, however, could not distinguish whether the reaction
acceleration was more due to increased ball impact, or due to a larger temperature increase when using a
heavier ball. In order to resolve this question, we conducted in situ investigation of the reaction involving
two 7 mm stainless steel balls at different temperatures. Whereas bulk sample temperature could not be
held constant due to imbalance between internal frictional heating and heat loss to the surroundings, the
experimental set-up allowed reactivity studies at the nominal temperatures of 50 °C, 65 °C, and 70 °C.
The in situ collected PXRD data reveals a change in reaction mechanism at elevated temperatures.
Disappearance of crystalline CdCl2 and cnge was now immediately accompanied by the rapid formation
of intermediate 2 as well as, more slowly, of 1 (Figure 2). Appearance of 2 was recognized by diffraction
lines in the time-resolved diffractogram matching those calculated from the known crystal structure
(CCDC code CDCACD01). For all reactions at elevated temperatures, the weight fraction of the
amorphous phase remained below 10%, as determined by Rietveld analysis. Upon complete
disappearance of crystalline CdCl2 the reaction mixture underwent a sharp transformation involving the
disappearance of 2 and rapid increase in content of 1. All reactions at elevated temperature exhibited this
sequence of transformations. Differences in the amorphous phase content between RT and hightemperature mechanochemical reactions can be tentatively explained by higher mobility of amorphous
phase at elevated temperatures, facilitating its crystallization into the final product 1 via the intermediate
2. Reaction at 50 °C corroborates these results, with reaction rates in between those at room temperature
and 65 C (Figure S3).
Detailed analysis of the reaction profiles is made challenging by reaction complexity, involving four or
five crystalline phases for room temperature and elevated temperature reactions respectively. Specifically,
reaction times at different temperatures are not strictly comparable due to the described change in
mechanism. However, Rietveld analysis reveals that weight fractions of crystalline CdCl 2 and of
crystalline 1 and 2 follow a linear pattern and the corresponding reaction rates are thus constant. These
common features allow a quantitative comparison of reactivity at different temperatures by describing the
change of the weight content (w) of crystalline CdCl2, 1 or 2 with time (t) using a linear expression w =
w0 + b×t, with w0 being the initial weight fraction of the crystalline phase and b the rate of its diminishing
for CdCl2 or formation for 1 and 2. (Figures S6-S9, Tables S1-S3).
Comparing the rate constant b across different experiments (Table 1) reveals that the rate of
disappearance of crystalline CdCl2 increases over 6-fold with temperature increase from RT to ca. 70 C,
which is consistent with the RT reaction achieving a constant composition after ca. 25 minutes, and the
reaction at 70 C reaching completion in 4 minutes (Figures 2c, d). The rate b for the linear segment of 1
and 2 formation also increases with temperature. The formation of 1 and 2 is, however, not suitable for
comparing chemical reactivity at different temperatures, as the formation of new crystalline phases is
dictated not only by a chemical reaction, but also by rates of crystal nucleation and growth.
Figure 2. Time-resolved powder X-ray diffractograms for the mechanochemical reaction conducted at
(left) 65 C and (right) at 70 C. Composition of reaction mixtures ceases to change after 8 minutes for
the reaction at 65 C and after 4 minutes for the reaction at 70 C. Calculated diffraction patterns for
products 1 (CCDC code MAKXON) and 2 (CCDC code CDCACD01) are shown above each
diffractogram. (b) Time-dependent change in weight fractions of all participating crystalline and
amorphous phases, established by Rietveld refinement of in situ collected PXRD data. Reliability of the
Rietveld refinement is reduced with increasing amount of 1, due to the overlap of the (111) reflection of
silicon standard with the group of reflections of 1 at around 2.6 in 2.
Table 1. Linear depletion (CdCl2) and growth (1, 2) constants for mechanochemical milling reactions at
different temperatures.a
CdCl2
1
2
Temperature
b (%/min)
(oC)
w0 (%)
b (%/min)
b (%/min)
RT
-1.5 ± 0.1
31.6 ± 0.7
-
-
RTb
-3.0 ± 0.1
30.6 ± 0.4
-
-
50
-4.8 ± 0.1
17.1 ± 0.3
1.3 ± 0.1
8.3 ± 0.2
65
-6.0 ± 0.1
28.1 ± 0.5
2.6 ± 0.1
9.5 ± 0.2
70
-9.2 ± 0.1
23.2 ± 0.2
4.1 ±0.1
13.4 ± 0.4
a) unless noted otherwise, milling was performed using two stainless steel balls of 7 mm diameter (weight
1.3 grams); b) milling was performed using one stainless steel ball of 9 mm diameter (weight 2.9 grams).
The apparently higher reactivity of anhydrous crystalline CdCl2 in a mixture with the crystalline hydrate
CdCl2H2O is surprising (Figures 2b, d, S1-S5). In all experiments at elevated temperatures where no or
little amorphization takes place,67 the content of CdCl2·H2O remains constant or changes only slightly
until all crystalline CdCl2 is depleted, after which the hydrate rapidly disappears. Such behaviour is
unusual when one considers that the apparently more reactive hydrate lays dormant, while the less reactive
anhydrous CdCl2 is being slowly consumed. Also, several earlier reports on mechanochemical
cocrystallization established that hydrates react faster than their anhydrous counterparts.68-72 This,
seemingly exceptional, behaviour can be explained by a mechanism in which CdCl 2H2O, rather than
CdCl2, reacts with cnge, releasing water that immediately reacts with anhydrous CdCl2 to regenerate the
CdCl2H2O phase (Scheme 2). The net outcome of such a mechanism is the depletion of anhydrous
crystalline CdCl2 and cnge accompanied by the formation of the coordination polymer product.
Scheme 2. Interconversion of CdCl2 and CdCl2H2O in milling synthesis of coordination polymers with
cnge.
To verify the reactivity of anhydrous CdCl2 towards water, we obtained a fresh batch of anhydrous
CdCl2. Preliminary PXRD analysis of this material revealed it was already completely converted into
CdCl2·H2O, attesting to the high reactivity of CdCl2 towards water. Next, we prepared crystalline CdCl2
by dehydration of CdCl2·H2O at 180 °C. The material was highly hygroscopic, reacting with air moisture
within minutes to yield CdCl2·H2O. Milling of freshly prepared anhydrous CdCl2 with cnge for 30
minutes at room temperature did not lead to product formation, whereas CdCl2·H2O readily reacted to
form 1 by milling for 30 minutes at room temperature. These observations fully confirm the proposed
mechanism in which the mechanochemical reaction proceeds via depletion of CdCl 2·H2O, which is
immediately replenished by the reaction of released water with remaining anhydrous CdCl 2. This
mechanism also explains rapid product formation upon complete disappearance of anhydrous CdCl2.
Namely, the reaction before the disappearance of CdCl2 is a neat grinding process, where water released
in the reaction of CdCl2·H2O is immediately bound again. However, once anhydrous CdCl2 has been
completely consumed, reaction of CdCl2·H2O results in a net release of water, transforming the reaction
into a rapid liquid-assisted grinding process.73-75
While it was previously proposed76 by the Boldyreva group that the formally neat mechanochemical
reactions of solvated reactants are effectively liquid-assisted processes facilitated by the liquid released
during the advancing reaction, the herein provided in situ and real time measurements are the first direct
experimental confirmation of such a reaction mechanism.
CONCLUSION
This study established the possibility to conduct in situ monitoring of mechanochemical milling
reactions at different temperatures. Despite difficulty in maintaining a constant temperature throughout
each experiment, this first variable-temperature real-time observation reveals remarkable thermal
sensitivity of a mechanochemical reaction of coordination polymer synthesis. For the model synthesis of
the coordination polymer Cd(cnge)2Cl2, a modest 45 C increase in bulk temperature resulted in a 6-fold
decrease in reaction time, a commensurate increase in reactant consumption rate, as well as a change in
reaction mechanism. Such high sensitivity of reaction kinetics to a relatively mild temperature increase
offers fundamentally important insight into mechanisms of mechanochemical reactions. Reactions by
milling are sometimes described by the "hot-spot" and "magma-plasma" models,77,78 which attribute
reactivity to reactant activation by highly localized, short-lived extreme increases in temperature resulting
from the impact of grinding media. Using inorganic salt metathesis in a planetary mill as a model system,
such hot-spots have been evaluated to be ca. 1 µm2 in size, reaching temperatures of up to 1000 C, over
ca. 10 ns. If such short-lived rises in temperature were the dominant factor in mechanosynthesis of
Cd(cnge)2Cl2, varying the bulk reaction mixture temperature by 45 C should not have a substantial
effect on reaction rates. Demonstrated thermal sensitivity of reaction kinetics47 indicates that the hot-spot
model of mechanochemical reactivity, which has been developed in the contexts of inorganic materials,
alloying and mineral processing, may not be adequate for the mechanochemistry of softer materials, such
as coordination polymers or cocrystals. This conclusion is consistent with the recent investigation of
Diels-Alder reactions of organic solids by the Mack group, who established that temperatures of hot spots
during milling of an organic material are likely to be below 100 C.79 Herein presented results open an
unprecedented, simple route for in situ and real-time explorations of mechanochemical reactivity at
different temperatures. We are currently improving the instrumentation for more accurate temperature
monitoring and control.
ASSOCIATED CONTENT
Supporting Information
Quantitative Rietveld plots, kinetic modeling and thermal analysis data. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
* Krunoslav Užarević, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000, Zagreb, Croatia. E-mail:
[email protected];
*Tomislav Friščić, Department of Chemistry and FRQNT Centre for Green Chemistry and Catalysis,
801 Sherbrooke St. W. H3A 0B8 Montreal, Canada. E-mail: [email protected];
*Ivan Halasz, Ruđer Bošković Institute, Bijenička cesta 54, HR-10000, Zagreb, Croatia. E-mail:
[email protected];
Funding Sources
NSERC Discovery Grant, the FRQNT Nouveaux Chercheurs program; Tak-Hing (Bill) and Christina
Chan Scholarship in Green Chemistry; the FRQNT Pre-doctoral Scholarship; and Marie Curie FP7PEOPLE-2011-COFUND program NEWFELPRO under Grant Agreement No. 62.
ACKNOWLEDGMENT
We are grateful to Mr. Vitomir Stanišić and Mr. Siniša Pecik (Ruđer Bošković Institute) for
manufacturing the PMMA reaction vessels and Mr. Tomislav Mrla (Ruđer Bošković Institute) and Mr.
Thomas Buslaps (ESRF, ID15) for assistance with the temperature measurement setup. Help of Dr
Simon A. J. Kimber (ESRF, ID15 beamline) in performing the experiments and insightful discussions
with Dr. Nikola Bregović (University of Zagreb) are gratefully acknowledged. We acknowledge the
financial support of the NSERC Discovery Grant, the FRQNT Nouveaux Chercheurs program, Ruđer
Bošković Institute, Center of Excellence for Advanced Materials and Sensors (Croatia) and McGill
University. C. M. acknowledges the Tak-Hing (Bill) and Christina Chan Scholarship in Green
Chemistry and the FRQNT Pre-doctoral Scholarship. The work of K. U. is supported under the
European Commission and the Croatian Ministry of Science, Education and Sports from the Marie
Curie FP7-PEOPLE-2011-COFUND program NEWFELPRO under Grant Agreement No. 62.
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FOR TABLE OF CONTENTS USE ONLY
Exploring the effect of temperature on a mechanochemical reaction by in situ
synchrotron powder X-ray diffraction
Krunoslav Užarević, Vjekoslav Štrukil, Cristina Mottillo, Patrick A. Julien, Andreas Puškarić,
Tomislav Friščić, Ivan Halasz
The first in situ and variable-temperature and real-time study of a milling reaction reveals a surprisingly
strong dependence of reaction mechanisms and rate on temperature. We provide also the first direct
evidence of how a formally dry milling reaction is facilitated by water released from a hydrated reactant.